CN102246042B - Sensing device for detecting target elements in a fluid - Google Patents
Sensing device for detecting target elements in a fluid Download PDFInfo
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- CN102246042B CN102246042B CN200980149704.2A CN200980149704A CN102246042B CN 102246042 B CN102246042 B CN 102246042B CN 200980149704 A CN200980149704 A CN 200980149704A CN 102246042 B CN102246042 B CN 102246042B
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54393—Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
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- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/551—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being inorganic
- G01N33/553—Metal or metal coated
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- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T29/00—Metal working
- Y10T29/49—Method of mechanical manufacture
- Y10T29/49002—Electrical device making
- Y10T29/49117—Conductor or circuit manufacturing
- Y10T29/49124—On flat or curved insulated base, e.g., printed circuit, etc.
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Abstract
The invention relates to a sensing device for sensing target elements in a fluid. The sensing device comprises a substrate (61) having first regions (66a) and second regions (66b). A patterned first layer (62) is provided on the substrate (61), wherein the patterned first layer (62) covers the second regions (66b) and does not cover the first regions (66a). In the first regions (66a) capture elements (64) are arranged for capturing the target elements. Such a sensing device allows defining the first regions, i.e. capture regions, by the patterned first layer.
Description
Technical field
The present invention relates to a kind of sensing device for the target element in test fluid and target element checkout equipment.The invention still further relates to a kind of method for the manufacture of sensing device.
Background technology
US 2002/0028463A1 discloses a kind of sensing device for the target element in test fluid, and wherein target element is caught by the capturing element be positioned on metal level.Therefore, the target element of catching also is positioned on metal level.Which has limited the detection method group that may be used for detecting the target element of catching, namely only have the different detection methods of limited quantity to may be used for accurately detecting the target element of catching.Such as, optical means must use radiation, and it must pass through fluid in the current situation before the target element of scan capture.This radiation by fluid scattering and/or absorption, thus can reduce the accuracy of detection of the target element of catching.
Summary of the invention
The object of this invention is to provide a kind of sensing device for the target element in test fluid, target element checkout equipment and manufacture method.
In a first aspect of the present invention, provide the sensing device of the target element that can be used in test fluid, wherein this sensing device comprises:
-there is the substrate of first area and second area;
Patterning ground floor on-substrate, it covers second area, and first area is not covered by this ground floor; And
-capturing element, it is arranged in the first region for acquisition target element, and wherein capturing element is applied by the in the first region and on the first layer providing package solution containing capturing element.
Patterning ground floor provides to provide the first area and capped second area that are not covered by this patterned layer on substrate.Not capped first area is used as trapping region and capturing element provides in first area.Because ground floor by known technology very controlled map patterning, thus very accurately can limit first area and thus very accurately limit the region comprising capturing element.This allows to improve the precision detecting the target element of catching.In addition, ground floor does not affect the detection method group that may be used for detecting the target element of catching usually, because capturing element is not positioned on ground floor, and freely can select the material of substrate, makes the detection method of wishing may be used for detecting the target element of catching.Such as, the material of substrate for visible transparent, thus can allow the target element that optical detection is caught when not needing radiation to pass through fluid before scanning target element.Therefore, described sensing device allows to use the different detection methods of larger quantity to be used for accurately detecting target element.
Described sensing device can be the device of the detecting unit comprised for detecting the target element of catching, or this sensing device can be device interactional with target element checkout equipment, described target element checkout equipment is suitable for detecting the target element of catching in sensing device.If sensing device comprises detecting unit, so it may further include attribute determining unit, and this attribute determining unit is used for the target element of catching based on detecting, and especially determines the attribute of fluid based on the amount of the target element of catching detected.If target element checkout equipment detects the target element of catching, so it may further include attribute determining unit, and this attribute determining unit is used for the target element of catching based on detecting, and especially determines the attribute of fluid based on the amount of the target element of catching detected.
Described sensing device preferably further comprises the stop second layer, and this stop second layer arranges and combines on the second region for minimizing capturing element on the first layer.This providing on the second barrier layer is favourable, because capturing element is attached to the probability reduced or is not attached in second area, namely capturing element will mainly or only provide in the first region.
This barrier layer preferably comprises hydrophilic material.
Preferably, pretreatment first area is to improve their binding ability in conjunction with capturing element.First area can be regulated to realize the even and/or intensive distribution of capturing element.
Preferably, described substrate is at least transparent at first area place.Further preferably, whole substrate is transparent.Transparent substrate is favourable, because it allows the target element of catching in optical detection sensing device.
Further preferably, ground floor is metal level.This metal level is preferably by means of soft lithography patterning.Metal is used to be favourable as ground floor, because particularly can very accurately patterned metal layer.Therefore, the precision of trapping region can be improved further and thus improve the precision of the detection of target element of catching.
Further preferably, capturing element is applied by being provided on substrate and ground floor by the solution comprising capturing element.Further preferably, capturing element is applied by printing the solution spot comprising capturing element.Single printing spot can cover multiple first area.Because first area (i.e. capture region) is limited by patterning ground floor, instead of limited by the accuracy of providing package containing the solution of capturing element, thus can reduce when not reducing the precision limiting capture region about the requirement of providing package containing the precision of the solution of target element.This allows to use the so not complicated method for providing solution, such as ink jet printing.
Further preferably, first area has rectangular shape.This allows the shape making first area to be suitable for by using CCD camera to detect target element.
Described sensing device preferably suitable for cooperating with target element checkout equipment so that the target element when capturing element allowing target element checkout equipment target element to be in a fluid arranged on first area place is caught in test fluid.This sensing device is the sensing box being such as suitable for can being inserted in target element checkout equipment.This allows to use disposable sensing device, and it can use together with identical target element checkout equipment.
In another aspect of this invention, provide a kind of target element checkout equipment for the target element in test fluid, wherein this target element checkout equipment is suitable for cooperate with sensing device, and wherein this sensing device comprises:
-there is the substrate of first area and second area,
Patterning ground floor on-substrate, it covers second area, and first area is not covered by this ground floor, and
-capturing element, it is arranged in the first region for acquisition target element, and wherein capturing element is applied by the in the first region and on the first layer providing package solution containing capturing element,
Target element when wherein the target element checkout equipment target element be suitable for the in a fluid capturing element be set up in the first region is caught in test fluid.
In another aspect of this invention, provide a kind of method of sensing device of the target element for the manufacture of can be used in test fluid, wherein the method comprising the steps of:
-substrate is provided,
-on substrate, provide ground floor,
-to ground floor patterning, obtain first area and second area, wherein second area is patterned ground floor and covers and first area is not patterned ground floor covers, and
-target element of the fluid of capturing element for catching in first area is provided, wherein provide capturing element by the first region and on the first layer providing package containing the solution of capturing element.
Should be understood that, the sensing device according to claim 1, the target element checkout equipment according to claim 10 and the method for the manufacture of sensing device according to claim 11 have the similar and/or identical preferred embodiment defined in dependent claims.
Should be understood that, the preferred embodiments of the present invention also can be dependent claims and any combination of corresponding independent claims.
Accompanying drawing explanation
These and other aspects of the present invention will be well-known according to embodiment described below, and set forth with reference to these embodiments.In the following figures:
Fig. 1 schematically and schematically illustrate the embodiment of sensing device,
Fig. 2 schematically and schematically illustrate the sectional view detecting surface,
Fig. 3 schematically and schematically illustrate the top view that another detects surface,
Fig. 4 schematically and schematically illustrate the sectional view of the embodiment of sensing box,
Fig. 5 schematically and schematically illustrate the embodiment of target element checkout equipment,
Fig. 6 schematically and schematically illustrate the magnetic-particle being attached to and detecting surface,
Fig. 7 shows the flow chart illustrated for the manufacture of the method for sensing device, and
Fig. 8 schematically and schematically illustrate the sectional view manufactured according to the detection surface during sensing device of the present invention.
Detailed description of the invention
Fig. 1 schematically and schematically illustrate the sensing device 20 of the target element that can be used in test fluid.Sensing device 20 comprises the fluid intake 21 for allowing in fluid inflow sensing chamber 22.Fluid comprises target element, and these target elements can be captured on the detection surface 23 of sensing chamber 22.Sensing device 20 also comprises the detecting unit 24 be suitable for by using detection bundle 27 to detect the target element that surface 23 is caught.Sensing device 20 also comprises the attribute determining unit 25 for the attribute based on the target element determination fluid of catching detected.The attribute determined by attribute determining unit 25 such as just detects the amount of the target element that surface 23 is caught.The attribute of fluid also can be, the amount of the target element of catching exceedes predefined threshold value.
Sensing device 20 comprises the output unit 26 of the signal of the attribute of the determination for exporting instruction fluid further.
In one embodiment, sensing device 20 does not comprise output unit 26 and attribute determining unit 25.In another embodiment, sensing device 20 does not even comprise detecting unit 24.The detection of the target element of catching can be performed by independent detection means.
Fig. 2 schematically and schematically illustrate the cross section detecting surface 23.Detection surface 23 comprises the stop second layer 63 on substrate 61, patterning ground floor 62 and patterning ground floor 62.Substrate 61 do not comprised capturing element 64 by those districts (first area 66a) that ground floor 62 covers.
Such as, by means of soft lithography, can in point-device mode to ground floor 62 patterning.In addition, soft lithography can allow the good restriction realizing first area shape.On the ground floor 62 that can be implemented as patterned metal layer, water wetted material can be applied stop the second layer 63 to be formed before capturing element is provided.It should be pointed out that capturing element substantially can only be attached to not to be covered, typically with metal layers to cover and thus not by region that water wetted material covers.Therefore, the precision of the shape of macular area can be high.
Fig. 3 schematically and schematically illustrate the top view on the detection surface according to another embodiment.Here, macular area SA1-SA9 is depicted.Around after the broken circle of macular area SA1-SA9 relates to ink jet printing can involved capturing element catch the district that spot covers.Visible for example, referring to macular area SA9, some first areas, are four first areas in this example, can be covered by a macular area simultaneously.
In Fig. 1 schematically and the sensing chamber 22 exemplarily illustrated can be in Fig. 4 schematically and a part for the sensing box 1 exemplarily illustrated.Sensing box 1 comprises optional filter element 2, and this filter element is for receiving fluid 3 and for filtering this fluid.Sensing box 1 comprises Part I 15 and Part II 16 and capillary structure, and this capillary structure comprises the capillary fluid passage 8 between Part I 15 and Part II 16.Fluid is directed into the detection position 7 which providing and detect surface 23 by capillary force.Part II 16 correspondence provides the substrate 61 of capturing element 64 thereon.In this embodiment, sensing box 1 comprises another filter element 9, and this filter element is used for filtering this fluid 3 when fluid 3 passes through fluid passage 8.In other embodiments, filter element 9 can be omitted.Sensing box 1 also comprises steam vent 17, and this steam vent leaves fluid passage 8 for allowing the air in fluid passage and/or in the fluid detecting position 7.
Fig. 5 schematically and schematically illustrate the cross section sensing box 1 shown in Fig. 4 of being inserted in target element checkout equipment 38.The target element when capturing element 64 at the 66a place, first area that target element checkout equipment 38 target element be suitable in a fluid is arranged on the detection surface 23 of sensing box 1 is caught in test fluid.
In this embodiment, target element checkout equipment 38 comprises magnetic element 39, and this magnetic element is provided for the magnetic field on the detection surface 23 of the Part II 16 of the magnetic-particle 45 arrival sensing box 1 forced in fluid passage 8.In this embodiment, by utilizing the light beam 49 produced by the light source 40 such as Laser Devices or LED to irradiate this surface and by being detected the magnetic-particle 45 detected from the light of this surface reflection surperficial 23 by detector 43.Detector 43 is such as the photoelectric detector as photodiode or the two-dimensional camera as CCD camera.Optical element 41 and 32 can be arranged in light beam 49 to produce directional light or focused beam 49 respectively.Optical element 41,32 is preferably lens.
The configuration of delineating in Fig. 5 shows the change using FTIR method (frustrated total internal reflection) to detect surface.If light beam has the medium of high index (such as Part II 16) and interface between having compared with the medium (such as fluid) of low-refraction is being reflected, so there is certain critical angle of incidence, more than this critical angle of incidence, there is the situation of total internal reflection (TIR).Current detection configuration (about refractive index and incidence angle) makes the total internal reflection that there is incident beam.Although light is totally reflected in this case, in the very thin layer of medium with low-refraction, still there is penetrating of light.This is called fadout light, and its intensity is exponentially decay in the low refractive index dielectric for optical wavelength magnitude in characteristic penetration depth.Therefore, in practice, penetration depth is preferably less than 0.5 micron.If magnetic-particle is attached to surface, so preferably the optical properties of this very thin first fluid layer of about 0.5 micron is changed, and causes the minimizing of the light beam reflected.This is caused by the absorption of fadout light and scattering.As a result, the signal of photoelectric detector changes.
The detection of target element such as can be measured by so-called sandwich and perform, and described sandwich measures carries out exemplary description hereinafter with reference to Fig. 6.Magnetic bead 45 is coated with specific antibody 57, and this specific antibody is attached to the target element 58 existed in fluid.When the magnetic bead freely existed in fluid and available target element react, these integuments are attracted to the detection surface 23 being coated with capturing element 64, and described capturing element is such as another antibody that can be coupled to target element.After the fully long reaction time, switching field, makes magnetic bead upwards be drawn, thus the pearl only with the specific binding of correct target element keeps being attached to surface.In this moment, fluorescence detector can be read out and provide the signal of the information of the amount of carrying about the target element detected on surface.Therefore, detect position, the first area namely detecting surface 23 can utilize the biosphere with antibody to cover.
Fig. 7 shows the flow chart illustrated for the manufacture of the method for the sensing device of the target element that can be used in test fluid.In a step 101, substrate 61 is provided.In a step 102, substrate 61 provides ground floor 62.In step 103, to ground floor 62 patterning, thus obtain first and second region 66a, 66b.Second area 66b is patterned ground floor 62 and covers and first area 66a is not patterned ground floor 62 covers.At step 104, ground floor 62 provides stop that the second layer 63 and this stop second layer are used for reducing the combination of capturing element in second area 66b.In step 105, in the 66a of first area, be provided for the capturing element of the target element of catching in fluid.
In step 103, ground floor can carry out patterning in point-device mode by soft lithography.In addition, soft lithography can allow the good restriction of the shape realizing first area (i.e. capture region).On the ground floor 62 that can be implemented as patterned metal layer, water wetted material can be applied at step 104 to form barrier layer 63.It should be pointed out that capturing element can mainly or only be attached to not covered by ground floor and thus not by region that water wetted material covers.
Substrate according to above-described embodiment can be transparent at least partly and may be used for detecting the target element in sample that is biological, environment or chemistry.Preferably, this substrate is a part for the sensing device as sensing box.On substrate or at substrate place, the structuring lid that can form fluid passage can be provided.Sensing device can comprise sample port and waste compartment.On substrate or in the fluid passage can apply any reagent to allow to realize the bioanalysis in closed system and/or biochemical analysis under moistening or drying regime.Alternatively, film heater and electrode can be integrated in substrate.
Above-described sensing device and/or target element checkout equipment can be used in molecular diagnosis and immune sensing field.Here, mensuration can be performed to the part in the district on the detection surface of sensing device.According to sensing device of the present invention can from printed circuit and the different array combination of catching detector as DNA array.Can be favourable according to sensing device of the present invention, because particularly when obtaining weak signal, the sensitivity of analysis can be improved.
Described capturing element can be linked to substrate by physical absorption or chemical reaction.
Fig. 8 schematically and during schematically illustrating manufacturing step 104, namely provide the sectional view on the detection surface during the step stopping the second layer 63.Detect the surperficial ground floor 62 comprised on substrate 61 and substrate 61.As has already been mentioned above, substrate 61 is preferably transparent carrier, and ground floor 62 is preferably the metal level as gold, aluminium, platinum, palladium etc.Ground floor 62 can such as by means of vapor deposition on substrate 61.However, it is noted that, also can apply other deposition process.The thickness of ground floor 62 is such as some nanometers.
In fig. 8, the detection surface during micro-contact printing MCP step is depicted.The imprinter 65 with the PDMS of structuring or patterned surface impregnated of the second barrier layer 63 such as formed by mercaptan.Imprinter 65 can be dried before being applied to ground floor 62.The patterned surface of imprinter 65 preferably can refer to the negative-appearing image of the pattern of the hope of ground floor 62.In other words, the surface of imprinter 65 can comprise recessed district 65a and convex region 65b.Recessed district 65a is corresponding with first area 66a, and convex region 65b is corresponding with second area 66b.When imprinter 65 is applied to the surface of ground floor 62 and is removed, form the self-assembled monolayer SAM of mercaptan.Typically, the material with ground floor 62 is formed chemical bond by mercaptan.Afterwards, preferably this surface can be etched by being immersed in etching bath on the surface of ground floor 62.In etching bath, those districts (first area 66a) do not covered by alkanethiol monolayer can be etched away, to expose the surface of substrate 61.In other words, exist wherein in those districts (second area 66b) on the second barrier layer 63 formed by mercaptan, do not etch away ground floor 62.On the other hand, between (namely there is no the second barrier layer 63) those districts (first area 66a) in, etch away ground floor 62.
Mercaptan can comprise the linear paraffinic hydrocarbons chain of several carbon atom length to have good etch-resistance.But these mercaptan may be hydrophobic and for may not be preferred in the present invention.On the other hand, diblock mercaptan comprises alkane chain near thiol group and the polyethylene glycol relative with thiol group (PEG) block.Therefore, the self-assembled monolayer with polyethylene glycol surface characteristic can be realized.Such self-assembled monolayer is enough for generation patterning ground floor, even if it only comprises the etch-resistance of reduction.But, this can not hinder it according to application of the present invention because only must thin layer be etched.
In the 66a of first area, such as by physical absorption, capturing element can be linked to substrate.Physical absorption can be used for antibody to be attached on polymer surfaces.Also by chemical reaction, capturing element can be linked to substrate to obtain the functionalized surfaces as epoxides or amine groups.These can be produced by the reaction with the chlorine or alkoxy silane with end epoxy or amine groups in surface.
But, also can apply other surface treatment to improve density and the function of capturing element.The deposition of ground floor 62 and patterning can perform before any surface treatment surface of execution.Thereafter, such as by means of printing process, such as, capturing element can be provided in the first region by ink jet printing.Here, the solution with capturing element can be applied to first area.It should be noted that size and the pattern in the region covered by capturing element can be determined by the pattern of ground floor 62.Any capturing element be applied to outside first area all can be flushed away, because they can not be attached to the surface of ground floor.Preferably, print spot and can cover the some first areas limited by patterning ground floor.Therefore, sub-spot pixelation is possible.In addition, the density of capturing element can evenly, because the edge limited by the dry edge of printing spot can be eliminated.And, can such as regulate the layout of first area to embody rectangular property.
The present invention relates to the thought of the pattern providing capturing element with fine definition, it has little feature and/or accurately or clearly border.Little feature is helpful in the accessibility improving the target element that will catch.Especially, the high-resolution providing patterned metal layer can improve sensor and without the need to applying capturing element based on high-resolution applying method.In other words, capturing element can be applied by means of ink jet printing.
Self-assembled monolayer (SAM) is provided to be favourable on the first layer, because micro-contact printing can be used for applying SAM.In addition, the SAM on ground floor can be used as resistant layer during etching ground floor.Preferably, SAM is hydrophilic.
In the above embodiments, ground floor 62 can be the metal level as gold, aluminium, palladium, platinum etc.In addition, mercaptan can be replaced by other functional groups reacted to the material of the layer selected.And PDMS can be replaced by another soft polymetric material as hydrogel.Ink jet printing can by cultivating (incubation), dipping in pen printing etc. replacement.Micro-contact printing can, serigraphy shaping by capillary or photoetching technique replace.Substrate can be the polymer of glass or injection moulding or extruding, such as PMMA, PS, PC, COP, PET.
Although in above-described embodiment, in other embodiments, this detection surface can be integrated in another sensing device in Fig. 2 schematically and the detection surface exemplarily illustrated is integrated in some sensing device.The present invention relates to any sensing device of the target element that can be used in test fluid, it comprises: the substrate with first area and second area; Patterning ground floor on substrate, it covers second area, and first area is not covered by ground floor; And capturing element, it is arranged in the first region for acquisition target element.In one embodiment, this sensing device can be only detect surface, and this detection surface is formed by following: the substrate with first area and second area; Patterning ground floor on substrate, it covers second area and first area is not covered by ground floor; And capturing element, it is arranged in the first region for acquisition target element.
Method according to the sensing device of the target element for the manufacture of can be used in test fluid of the present invention at least comprises step: provide substrate; Substrate provides ground floor; To ground floor patterning, obtain first area and second area, wherein second area is patterned ground floor and covers and first area is not patterned ground floor covers; And the target element of the fluid of capturing element for catching in first area is provided.In one embodiment, substrate provides ground floor and to ground floor patterning to obtain first area and second area can perform in a single step, wherein on substrate, provide patterning ground floor.If sensing device comprises more parts, method so for the manufacture of the sensing device of the target element that can be used in test fluid can comprise other step, such as, be integrated in sensing box by detection surface or be integrated in another more complicated sensing device.
The sensing device as sensing box for biology sensor or chemical sensor to be used in diagnostic field and can be used for detecting the low concentration analyzing thing in sample.These are analyzed thing and can be regarded as the target element that can capturing element be utilized on substrate to catch, and described capturing element is such as the antibody of protein detection, for the DNA/RNA strand of DNA/RNA detection or the molecule for drug test.And the biology sensor with multiloop loop system is known, wherein can detect different species simultaneously.A kind of position well limiting provide the method for different capture molecules to be printing process.If target molecule is attached to capturing element, any physical change obtained by this combination so can be detected.
Described sensing device can comprise the multiple interactional biomolecule arrays for monitoring between biomolecule simultaneously.
Described patterning ground floor can be compatible with many Cleaning Principle, and described Cleaning Principle in particular, for example uses the optical detection of fluorescence.
As has already been mentioned above, the second layer is preferably polyethylene glycol layer or another hydrophilic material.Capturing element is preferably antibody or oligonucleotides.
Described patterning ground floor can be suitable for the light in the region stopping to come Autonomous test surface or detect surface.
Described sensing device can be suitable for any detection suitably allowing to realize particle (particularly magnetic-particle) existence detecting on the surface or detect near surface based on any attribute of particle, such as, it can pass through Magnetic Methods (such as magnetic resistance, Hall effect, coil), optical means (such as imaging, fluorescence, chemiluminescence, absorb, scattering, evanescent field technology, surface plasmon resonance, Ramam effect etc.), sound detection (such as surface acoustic wave, bulk acoustic wave, cantilever, quartz crystal etc.), electrical detection (is such as conducted, impedance, ampere meter, redox cycle), its any combination etc. detects.
In one embodiment, target element is molecule target.Molecule target determines the larger concentration of part (such as cell, virus) and/or the share of existence or cell or virus, tissue extract etc. usually.
Target element can be processed before testing further.An example of further process is, (biology) chemistry of adding material or amendment target element or physical attribute are beneficial to detect.
Can use together with some biochemical measurement types according to device of the present invention, equipment and method, described biochemical measurement type is such as combine/dissociate mensuration, sandwich mensuration, competition assay, displacement mensuration, enzymatic determination etc.
Sensor multiplexed (i.e. the parallel use of different sensors and sensor surface), label multiplexed (the parallel use of namely dissimilar label) and room multiplexed (i.e. the parallel use of differential responses room) can be suitable for according to device of the present invention, method and apparatus.
The device described in the present invention, method and apparatus can be used as quick, the robust of small sample volumes and wieldy point of care biology sensor.Reative cell (namely sensing box) can be the disposable that will use together with compact reader, and namely described compact reader comprises the target element checkout equipment of one or more field generator for magnetic and one or more checkout gear.In addition, device of the present invention, method and apparatus can be used in the test of automation high-throughput.In this case, sensing chamber is installed to orifice plate in self-reacting device or test tube.
Magnetic bead above-mentioned or magnetic-particle are preferably nano particle, and it has scope at least one dimension between 3nm and 5000nm, preferably between 10nm and 3000nm, more preferably between 50nm and 1000nm.
Those skilled in the art urban d evelopment protect of the present invention time, according to the research for described accompanying drawing, present disclosure and claims, should understand and realize other modification to disclosed embodiment.
In detail in the claims, word " comprises/comprises " element or step of not getting rid of other, and indefinite article " " does not get rid of plural number.
Individual unit or device can realize the function of some that list in claim.State this pure fact of some measure in mutually different dependent claims and do not mean that the combination of these measures cannot advantageously be used.
Any Reference numeral in claim should not be regarded as the restriction to scope.
Claims (11)
1. can be used for a sensing device for the target element in test fluid, comprising:
-there is the substrate (61) of first area (66a) and second area (66b);
Patterning ground floor (62) on-substrate (61), it covers second area (66b), and first area (66a) is not covered by this ground floor (62); And
-capturing element (64), be arranged on for acquisition target element in first area (66a), wherein first area (66a) limited by patterning ground floor (62) and capturing element (64) by applying in first area (66a) and at the solution of the upper providing package of ground floor (62) containing capturing element (64).
2., according to the sensing device of claim 1, comprise further:
Stop the second layer (63), be arranged on ground floor (62) and be combined in second area (66b) for minimizing capturing element.
3., according to the sensing device of claim 2, wherein stop that the second layer (63) comprises hydrophilic material.
4., according to the sensing device of claim 1, wherein pretreatment first area (66a) is to improve their binding ability in conjunction with capturing element.
5., according to the sensing device of claim 1, wherein substrate (61) is at least transparent at first area (66a) place.
6., according to the sensing device of claim 1, wherein ground floor (62) is metal level.
7. according to the sensing device of claim 1, the solution spot wherein comprising capturing element (64) by printing applies capturing element (64), and wherein single printing spot covers multiple first area (66a).
8., according to the sensing device of claim 1, wherein first area (66a) has rectangular shape.
9., according to the sensing device of claim 1, wherein this sensing device (1) is suitable for cooperate with target element checkout equipment (38) so that the target element when capturing element (64) allowing target element checkout equipment (38) target element to be in a fluid arranged on first area (66a) place is caught in test fluid.
10., for a target element checkout equipment for the target element in test fluid (3), wherein this target element checkout equipment (38) is suitable for cooperate with sensing device (1), and wherein this sensing device (1) comprising:
-there is the substrate (61) of first area (66a) and second area (66b),
Patterning ground floor (62) on-substrate (61), it covers second area (66b), and first area (66a) is not covered by this ground floor (62), and
-capturing element (64), be arranged in first area (66a) for acquisition target element, wherein first area (66a) limited by patterning ground floor (62) and capturing element (64) by applying in first area (66a) and at the solution of the upper providing package of ground floor (62) containing capturing element (64)
Target element when wherein target element checkout equipment (38) target element be suitable for the in a fluid capturing element (64) be arranged in first area (66a) is caught in test fluid.
11. 1 kinds, for the manufacture of the method for the sensing device of the target element that can be used in test fluid, comprise step:
-substrate (61) is provided;
-on substrate (61), provide ground floor (62);
-to ground floor (62) patterning, obtain first area (66a) and second area (66b), wherein second area (66b) is patterned ground floor (62) and covers and first area (66a) is not patterned ground floor (62) covering; And
-target element of the fluid of capturing element (64) for catching in first area (66a) is provided, wherein first area (66a) is limited by patterning ground floor (62) and by providing capturing element (64) containing the solution of capturing element (64) in first area (66a) and at the upper providing package of ground floor (62).
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08171277 | 2008-12-11 | ||
| EP08171277.0 | 2008-12-11 | ||
| PCT/IB2009/055496 WO2010067279A1 (en) | 2008-12-11 | 2009-12-04 | Sensing device for detecting target elements in a fluid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102246042A CN102246042A (en) | 2011-11-16 |
| CN102246042B true CN102246042B (en) | 2015-04-29 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200980149704.2A Active CN102246042B (en) | 2008-12-11 | 2009-12-04 | Sensing device for detecting target elements in a fluid |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20110236261A1 (en) |
| EP (1) | EP2380022B1 (en) |
| JP (1) | JP5543485B2 (en) |
| CN (1) | CN102246042B (en) |
| WO (1) | WO2010067279A1 (en) |
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|---|---|---|---|---|
| ES2857574T3 (en) * | 2015-07-23 | 2021-09-29 | Adarza Biosystems Inc | Competitive Small Molecule Detection Assays Using Array Imaging Reflectometry |
Citations (3)
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| CN1460723A (en) * | 2002-05-15 | 2003-12-10 | 三星电子株式会社 | Method for preparing biomolecule chip flat-plate with hydrophilic and lipophilic area |
| CN1598575A (en) * | 2003-09-18 | 2005-03-23 | 中国科学院力学研究所 | Method for making bio-chip |
| CN1645147A (en) * | 2005-01-18 | 2005-07-27 | 南开大学 | Protein chip for immune analysis |
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|---|---|---|---|---|
| US5776748A (en) * | 1993-10-04 | 1998-07-07 | President And Fellows Of Harvard College | Method of formation of microstamped patterns on plates for adhesion of cells and other biological materials, devices and uses therefor |
| US5512131A (en) * | 1993-10-04 | 1996-04-30 | President And Fellows Of Harvard College | Formation of microstamped patterns on surfaces and derivative articles |
| US6368877B1 (en) * | 1997-06-25 | 2002-04-09 | Massachusetts Institute Of Technology | Self-assembling peptide surfaces for cell patterning and interactions |
| DE69841171D1 (en) * | 1997-08-01 | 2009-11-05 | Canon Kk | Reaction site array, process for its preparation, reaction process under its use and quantitative determination method for a substance in a sample solution using it |
| JP2004522935A (en) * | 2000-08-14 | 2004-07-29 | サーフェイス ロジックス，インコーポレイティド | Biomolecule array |
| US20020164824A1 (en) * | 2001-02-16 | 2002-11-07 | Jianming Xiao | Method and apparatus based on bundled capillaries for high throughput screening |
| JP2006132943A (en) * | 2004-11-02 | 2006-05-25 | Sumitomo Bakelite Co Ltd | Method of manufacturing biochip |
| JP4626377B2 (en) * | 2005-04-26 | 2011-02-09 | セイコーエプソン株式会社 | Target molecule detection method, gene polymorphism detection method, and substrate and kit used in these detection methods |
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2009
- 2009-12-04 CN CN200980149704.2A patent/CN102246042B/en active Active
- 2009-12-04 JP JP2011540288A patent/JP5543485B2/en not_active Expired - Fee Related
- 2009-12-04 EP EP09787377.2A patent/EP2380022B1/en not_active Not-in-force
- 2009-12-04 US US13/133,345 patent/US20110236261A1/en not_active Abandoned
- 2009-12-04 WO PCT/IB2009/055496 patent/WO2010067279A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1460723A (en) * | 2002-05-15 | 2003-12-10 | 三星电子株式会社 | Method for preparing biomolecule chip flat-plate with hydrophilic and lipophilic area |
| CN1598575A (en) * | 2003-09-18 | 2005-03-23 | 中国科学院力学研究所 | Method for making bio-chip |
| CN1645147A (en) * | 2005-01-18 | 2005-07-27 | 南开大学 | Protein chip for immune analysis |
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Also Published As
| Publication number | Publication date |
|---|---|
| JP5543485B2 (en) | 2014-07-09 |
| EP2380022A1 (en) | 2011-10-26 |
| WO2010067279A1 (en) | 2010-06-17 |
| US20110236261A1 (en) | 2011-09-29 |
| CN102246042A (en) | 2011-11-16 |
| JP2012511718A (en) | 2012-05-24 |
| EP2380022B1 (en) | 2017-04-05 |
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